Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair
Abstract Background The aim of this study was to assess the safety and efficacy of human umbilical cord mesenchymal stromal cells (hUC-MSCs) patch used as an adjuvant therapy in fetal myelomeningocele (MMC) surgery in the ovine model. Methods hUC-MSCs were isolated from human umbilical cords (UC) us...
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BMC
2024-11-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-024-03991-y |
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| author | Yoann Athiel Laura Cariot Jean-Marie Jouannic Corentin Maillet Vincent Mauffré Clovis Adam Hélène Huet Jérôme Larghero Justine Nasone Lucie Guilbaud |
| author_facet | Yoann Athiel Laura Cariot Jean-Marie Jouannic Corentin Maillet Vincent Mauffré Clovis Adam Hélène Huet Jérôme Larghero Justine Nasone Lucie Guilbaud |
| author_sort | Yoann Athiel |
| collection | DOAJ |
| description | Abstract Background The aim of this study was to assess the safety and efficacy of human umbilical cord mesenchymal stromal cells (hUC-MSCs) patch used as an adjuvant therapy in fetal myelomeningocele (MMC) surgery in the ovine model. Methods hUC-MSCs were isolated from human umbilical cords (UC) using the explant method, cultured and characterized. hUC-MSCs were then embedded in a fibrin patch. MMC were surgically created at 75 days of gestation and repaired at 89 days of gestation in sheep fetuses. Two groups were compared: the hUC-MSCs group in which MMC was repaired using a cellular patch and the control group, in which MMC was repaired using an acellular patch. Safety was evaluated by clinical ewes’ monitoring during gestation, and clinical and histological examinations of lambs after birth. Efficacy was assessed by clinical neurological evaluation at 2 and 24 h of life using the sheep locomotor rating scale and by histological analyses. Results Among the 17 operated lambs, nine were born alive: six in the hUC-MSCs group and three in the control group. Overall fetal loss was 47% (8/17) without differences between the two groups. No fever was reported in ewes. No tumors were detected in clinical and histological examinations in the lambs. At 24 h of life, mean Sheep Locomotor Rating score was higher in the hUC-MSCs group than in the control group: 15.0 versus 2.0 (p = 0.07). Histological analyses showed a higher large neurons density in the hUC-MSCs group in comparison with the control group: 9.9 versus 6.3/mm2 of gray matter (p = 0.04). Lambs in the hUC-MSCs group had lower fibrosis around the spinal cord and at the level of the MMC scar: 70.9 versus 253.7 μm (p = 0.10) and 691.3 versus 1684.4 μm (p = 0,18), respectively. Conclusions Ovine fetal repair of MMC using human UC-MSCs seems to be an effective and safe procedure. |
| format | Article |
| id | doaj-art-12155f64f8fb4eef85111e1a86cbee4c |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj-art-12155f64f8fb4eef85111e1a86cbee4c2024-11-24T12:13:33ZengBMCStem Cell Research & Therapy1757-65122024-11-011511810.1186/s13287-024-03991-ySafety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repairYoann Athiel0Laura Cariot1Jean-Marie Jouannic2Corentin Maillet3Vincent Mauffré4Clovis Adam5Hélène Huet6Jérôme Larghero7Justine Nasone8Lucie Guilbaud9Service de médecine foetale, DMU ORIGYN, APHP, Hôpital Trousseau, Sorbonne UniversitéService de médecine foetale, DMU ORIGYN, APHP, Hôpital Trousseau, Sorbonne UniversitéService de médecine foetale, DMU ORIGYN, APHP, Hôpital Trousseau, Sorbonne UniversitéService de médecine foetale, DMU ORIGYN, APHP, Hôpital Trousseau, Sorbonne UniversitéÉcole Nationale Vétérinaire d’AlfortService d’anatomopathologie, Hôpital BicêtreÉcole Nationale Vétérinaire d’AlfortUnité de Thérapie Cellulaire, Université Paris Cité, AP-HP, Hôpital Saint-Louis, U976 et CIC de Biothérapies, INSERMUnité de Thérapie Cellulaire, Université Paris Cité, AP-HP, Hôpital Saint-Louis, U976 et CIC de Biothérapies, INSERMService de médecine foetale, DMU ORIGYN, APHP, Hôpital Trousseau, Sorbonne UniversitéAbstract Background The aim of this study was to assess the safety and efficacy of human umbilical cord mesenchymal stromal cells (hUC-MSCs) patch used as an adjuvant therapy in fetal myelomeningocele (MMC) surgery in the ovine model. Methods hUC-MSCs were isolated from human umbilical cords (UC) using the explant method, cultured and characterized. hUC-MSCs were then embedded in a fibrin patch. MMC were surgically created at 75 days of gestation and repaired at 89 days of gestation in sheep fetuses. Two groups were compared: the hUC-MSCs group in which MMC was repaired using a cellular patch and the control group, in which MMC was repaired using an acellular patch. Safety was evaluated by clinical ewes’ monitoring during gestation, and clinical and histological examinations of lambs after birth. Efficacy was assessed by clinical neurological evaluation at 2 and 24 h of life using the sheep locomotor rating scale and by histological analyses. Results Among the 17 operated lambs, nine were born alive: six in the hUC-MSCs group and three in the control group. Overall fetal loss was 47% (8/17) without differences between the two groups. No fever was reported in ewes. No tumors were detected in clinical and histological examinations in the lambs. At 24 h of life, mean Sheep Locomotor Rating score was higher in the hUC-MSCs group than in the control group: 15.0 versus 2.0 (p = 0.07). Histological analyses showed a higher large neurons density in the hUC-MSCs group in comparison with the control group: 9.9 versus 6.3/mm2 of gray matter (p = 0.04). Lambs in the hUC-MSCs group had lower fibrosis around the spinal cord and at the level of the MMC scar: 70.9 versus 253.7 μm (p = 0.10) and 691.3 versus 1684.4 μm (p = 0,18), respectively. Conclusions Ovine fetal repair of MMC using human UC-MSCs seems to be an effective and safe procedure.https://doi.org/10.1186/s13287-024-03991-yMyelomeningoceleFetal repairUmbilical cord-mesenchymal stromal cellsSafetyEfficacy |
| spellingShingle | Yoann Athiel Laura Cariot Jean-Marie Jouannic Corentin Maillet Vincent Mauffré Clovis Adam Hélène Huet Jérôme Larghero Justine Nasone Lucie Guilbaud Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair Stem Cell Research & Therapy Myelomeningocele Fetal repair Umbilical cord-mesenchymal stromal cells Safety Efficacy |
| title | Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair |
| title_full | Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair |
| title_fullStr | Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair |
| title_full_unstemmed | Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair |
| title_short | Safety and efficacy of human umbilical cord-derived mesenchymal stromal cells in fetal ovine myelomeningocele repair |
| title_sort | safety and efficacy of human umbilical cord derived mesenchymal stromal cells in fetal ovine myelomeningocele repair |
| topic | Myelomeningocele Fetal repair Umbilical cord-mesenchymal stromal cells Safety Efficacy |
| url | https://doi.org/10.1186/s13287-024-03991-y |
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